This research will elucidate the mechanisms of inflammatory cell accumulation at sites of immunological reactions. The means by which polymorphonuclear leukocytes (PMNs) and macrophages perceive chemical gradients will be determined. Receptors for the N-formylated peptide chemotactic factors will be characterized on inflammatory cells. The regulation of receptor expression on intact leukocytes will be determined. We will see if exposure of leukocytes to chemoattractants causes enhanced or depressed chemotactic factor expression on the cell surface. These phenomena, termed "up" regulation and "down" regulation (desensitization) may allow the cells to respond and adapt to chemotactic gradients. The role of receptor density, motility and cellular localization for the biological activities of PMNs will be determined. chemotaxis, lysosomal enzyme secretion and oxygen radical production by leukocytes will be examined to see if these responses have similar or different requirements in terms of receptor number or distribution. The signals which transduce the information conveyed by chemotactic factor receptor occupancy on leukocytes will be defined. It will be seen if the signals required for secretion and superoxide anion production are the same as those required for directed migration. The role of specific transmethylation reactions in the biological responses of leukocytes will be elucidated. The relationship between chemotaxis, phospholipid methylation, and cytoskeletal assembly will be studied. The differentiation of a non-chemotactically responsive human monocyte-like cell line (U937) into a responsive cell upon incubation with lymphokines will be studied and the lymphokine which induces the differentiation of this cell line, will be characterized. Finally, the molecular basis of defects in leukocyte function associated with depressed and elevated chemotactic responses in humans will be studied. We will determine if abnormal chemotactic responses associated for example, with juvenile periodontities, psoriatic arthritis and Chediak-Higashi syndrome are related to abnormal expression of function of chemotactic factor receptors, transmethylation reactions or other biochemical processes known to be involved in the chemotactic response.